Solubilized CoQ-10 and carnitine

ABSTRACT

The present invention is directed to compositions and methods of delivery of CoQ-10 and an amino acid solubilized in monoterpenes. Use of monoterpenes as dissolving agents, greatly effects the ability to incorporate greater amounts of bioactive CoQ-10 and the amino acid, such as carnitine, i.e., carnitine tartrate, in formulations, such as soft gel capsules.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a continuation-in-part of U.S. application Ser. No.10/674,268, filed on Sep. 29, 2003, entitled “Solubilized CoQ-10”, thecontents of which are incorporated herein in their entirety byreference.

FIELD OF THE INVENTION

The present invention relates to the solubilization of coenzyme Q-10 andanalogs thereof and/or carnitine and analogs thereof in at least onemonoterpene, thereby providing increased bioavailability in delivery.

BACKGROUND OF THE INVENTION

CoQ-10 (coenzyme Q10) is a fat-soluble quinone that is structurallysimilar to vitamin K and commonly known as ubiquinone. CoQ-10 is foundin most living organisms, and is essential for the production ofcellular energy. CoQ-10 (2,3 dimethyl-5 methyl-6-decaprenylbenzoquinone) is an endogenous antioxidant found in small amounts inmeats and seafood. Although CoQ-10 is found in all human cells, thehighest concentrations of CoQ-10 occur in the heart, liver, kidneys, andpancreas. It is found naturally in the organs of many mammalian species.

CoQ-10 can be synthesized in the body or it can be derived from dietarysources. Situations may arise, however, when the need for CoQ-10surpasses the body's ability to synthesize it. CoQ-10 can be absorbed byoral supplementation as evidenced by significant increases in serumCoQ-10 levels after supplementation.

CoQ-10 is an important nutrient because it lies within the membrane of acell organelle called the mitochondria. Mitochondria are known as the“power house” of the cell because of their ability to produce cellularenergy, or ATP, by shuttling protons derived from nutrient breakdownthrough the process of aerobic (oxygen) metabolism. CoQ-10 also has asecondary role as an antioxidant. CoQ-10, due to the involvement in ATPsynthesis, affects the function of almost all cells in the body, makingit essential for the health of all human tissues and organs. CoQ-10particularly effects the cells that are the most metabolically active:heart, immune system, gingiva, and gastric mucosa

Several clinical trials have shown CoQ-10 to be effective in supportingblood pressure and cholesterol levels. Furthermore, CoQ-10 has also beenshown to improve cardiovascular health. CoQ-10 has been implicated asbeing an essential component in thwarting various diseases such ascertain types of cancers. These facts lead many to believe that CoQ-10supplementation is vital to an individual's well being.

CoQ-10 is sparingly soluble in most hydrophilic solvents such as water.Therefore, CoQ-10 is often administered in a powdered form, as in atablet or as a suspension. However, delivery of CoQ-10 by these methodslimits the bioavailability of the material to the individual.

Carnitine is a water-soluble vitamin like compound that the bodyutilizes to turn fat into energy. Carnitine works as part of anenzymatic complex formed from carnitine acyltransferase 1, carnitinetranslocase and carnitine transferase 11.

Carnitine is often used for heart conditions and it may be useful totreat angina or chest pain. Research has also shown that carnitine isalso useful in the treatment of congestive heart failure andintermittent claudication. Although carnitine does not increase bloodflow, it is believe that it helps muscles to better function underdifficult painful circumstances, such as those associated withclaudication.

The actions of carnitine and CoQ-10 are interrelated. In fact,carnitine, through beta-oxidation of fatty acids, is able to restore theenergy supplies necessary for cell-life, whereas Coenzyme Q is able torestore the ATP supplies necessary for the energetic metabolic processesof the cell.

There is a need in the art for an improved methodology to deliverincreased amounts of bioavailable CoQ-10 and/or an amino acid, such ascarnitine to an individual in need thereof.

BRIEF SUMMARY OF THE INVENTION

The present invention pertains to the surprising discovery thatubiquinone (CoQ-10) and an amino acid such as carnitine can be readilydissolved in varying concentrations in a monoterpene. Generally, untilthe present discovery, most liquid delivery methods used for eitherCoQ-10 and/or an amino acid such as carnitine could solubilize only upto about 5% by weight of the CoQ-10 in the “solvent”. Typical solventsincluded various oils or the combination of CoQ-10 and amino acid(s) washeld in an aqueous suspension. The present invention provides theability to solubilize both CoQ-10 and/or an amino acid such as carnitinein at least one monoterpene in concentrations of up to about 60% (weightto weight) without the need to aggressively heat the solution or withgentle warming. In particular, the solubilization of the CoQ-10 and/oramino acid with a monoterpene can be accomplished at ambienttemperatures.

In one aspect, the present invention pertains to compositions thatinclude coenzyme Q-10 or an analog thereof and/or an amino acid (oranalog thereof, i.e., carnitine) with a sufficient quantity of amonoterpene that is suitable to solubilize said coenzyme Q-10, and/or anamino acid and, optionally, a pharmaceutically acceptable carrier.Generally, about 30 to about 45% of the CoQ-10 (by weight) issolubilized in the monoterpene and between about 0.5% to about 20% ofthe amino acid is solubilized (by weight) in the monoterpene. Inparticular, the range of the amino acid, such as a carnitine, is betweenabout 0.2 to about 15%, more particularly, between about 0.5 and 10%,and even more particularly, between about 1.0% and about 2.0% (by weightof amino acid). In one particular aspect, the monoterpene is limonene.The compositions of the invention are useful as dietary supplements oras nutriceuticals.

In particular, the compositions of the invention are included in a softgelatin (soft gel) capsule. Typically, the soft gelatin capsule includesat least 5% by weight of coenzyme Q-10 or an analog thereof and/or atleast about 1.5 to about 2% by weight of an amino acid, i.e., carnitineor an analog thereof, solubilized in at least one monoterpene. Typicalmonoterpenes include, for example, perillyl alcohol, perillic acid,cis-dihydroperillic acid, trans-dihydroperillic acid, methyl esters ofperillic acid, methyl esters of dihydroperillic acid, limonene-2-diol,uroterpenol, and combinations thereof.

In another embodiment, the present invention pertains to methods fordelivery of an effective amount of bioavailable CoQ-10 and/or an aminoacid, such as carnitine, to an individual. The method includes providingCoQ-10 and/or an amino acid solubilized in a monoterpene, such that aneffective amount of CoQ-10 and/or an amino acid is provided to theindividual.

In still another embodiment, the present invention also includespackaged formulations of the invention that include at least onemonoterpene as a solvent for CoQ-10 and/or an amino acid andinstructions for use of the tablet, capsule, elixir, etc.

While multiple embodiments are disclosed, still other embodiments of thepresent invention will become apparent to those skilled in the art fromthe following detailed description, which shows and describesillustrative embodiments of the invention. As will be realized, theinvention is capable of modifications in various obvious aspects, allwithout departing from the spirit and scope of the present invention.Accordingly, the drawings and detailed description are to be regarded asillustrative in nature and not restrictive.

DETAILED DESCRIPTION

The present invention pertains to the surprising discovery thatubiquinone (CoQ-10) and/or an amino acid such as carnitine can bereadily dissolved in varying concentrations in various monoterpenes.CoQ-10 is found in most living organisms, and is essential for theproduction of cellular energy. Ubiquinone is a naturally occurringhydrogen carrier in the respiratory chain (coenzyme Q) and structurally,it is a 2,3-dimethoxy-5-methyl-1, 4-benzoquinone with a multiprenyl sidechain, the number of isoprene units varying depending upon the organismfrom which it is derived. CoQ-10 analogs include reduced andsemi-reduced CoQ-10 and ubiquinone derivatives described, for example,in WO 8803015, the teachings of which are incorporated herein byreference.

L-carnitine is recognized in the art and facilitates transport ofmaterials through the mitochondrial membrane. L-carnitine is anessential fatty acid metabolism cofactor that helps to move fatty acidsto the mitochondria from the cytoplasm. This is an important factor asthis is where CoQ-10 uptake occurs.

In one aspect of the present invention, L-carnitine is included in softgel formulations in combination with CoQ-10. Suitable ratios ofL-carnitine and CoQ-10 are known in the art and include those describedin U.S. Pat. No. 4,599,232, issued to Sigma Tau Industrie FaramaceuticheRiunite S.p.A. on Jul. 8, 1986, the teachings of which are incorporatedherein in their entirety. In particular, combinations of limonene,CoQ-10 and L-carnitine in soft gel formulations are of importance. Thepresent invention provides the advantage of solvating large amounts(relative to that of current state of the art) of CoQ-10 in limonene ina soft gel capsule along with an additive, such as L-carnitine.

It should be understood, that throughout the specification, reference ismade to CoQ-10 or amino acids, such as carnitine, and that suchreference includes the analogs thereof.

Generally, until the present discovery, most liquid delivery methodscould solubilize only up at most about 10% by weight of the CoQ-10and/or an amino acid in the “solvent. Typical solvents included oils or,for example, the CoQ-10 was held in an aqueous suspension.Alternatively, the CoQ-10 and/or the amino acid were provided as a solidin a tablet or powder.

The present invention provides the ability to solubilize CoQ-10 and/oramino acids in a monoterpene, as defined herein, in concentrations of upto about 60% (weight to weight) without the need to heat the solution.In one aspect, the monoterpene solubilizes CoQ-10 from about 0.1 percentby weight to about 45 percent by weight.

In particular, the solubilization of the CoQ-10 with monoterpenes can beaccomplished at ambient temperatures. In one aspect, from about 5 toabout 50 percent (weight CoQ-10/weight solvent) CoQ-10 can besolubilized in a monoterpene. In another aspect, from about 15 to about40 percent w/w can be solubilized and in still another aspect, fromabout 20 to about 35 percent w/w CoQ-10 can be solubilized in amonoterpene.

In another aspect, the solubilization of an amino acid or an amino acidanalog, such as carnitine, with one or more monoterpenes can beaccomplished at ambient temperatures. In one aspect, from about 0.05 toabout 0.5 percent (weight amino acid/weight solvent) amino acid can besolubilized in a monoterpene. In another aspect, from about 0.01 toabout 0.25 percent w/w can be solubilized and in still another aspect,from about 0.02 to about 0.2 percent w/w amino acid can be solubilizedin a monoterpene.

The term “amino acid” as used herein includes, but is not limited to,glycine, the L forms of alanine, valine, leucine, isoleucine,phenylalanine, tyrosine, proline, hydroxyproline, serine, threonine,cysteine, cystine, methionine, tryptophan, aspartic acid, glutamic acid,arginine, lysine, histidine, ornithine, hydroxylysine, carnitine, andother naturally occurring amino acids and analogs thereof.

For example amino acid analogs, such as carnitine “analogs” includeacetylated products, fumarate derivatives and the like, and acceptableammonium and metal salts thereof.

The term “carnitine” is also known as3-Carboxy-2-hydroxy-N,N,N-trimethyl-1-propanaminium hydroxide, innersalt; (3-carboxy-2-hydroxypropyl)trimethylammonium hydroxide, innersalt; gamma-amino-beta-hydroxybutyric acid trimethylbetaine;gamma-trimethyl-beta-hydroxybutyrobetaine;3-hydroxy-4-(trimethyl-ammonio)butanoate. See The Merck Index (1989), p.281 and references cited therein. Therefore, “carnitine” and “carnitineanalogs” includes, but is not limited to racemic or essentially pureL-carnitine (carnitine), or a corresponding alkanoyl-carnitine such ase.g. acetyl-carnitine or propionyl-carnitine, or a suitable salt of suchcompounds such as e.g. L-carnitine tartrate, L-carnitine fumarate,L-carnitine-magnesium-citrate, acetyl-L-carnitine tartrate,acetyl-L-carnitine-magnesium-citrate, or any mixture of the aforementioned compounds.

Carnitine and carnitine analogs also include those described in U.S.Pat. Nos. 5,362,753, 4,687,782, 5,030,458, 5,030,657, 4,343,816,5,560,928, 5,504,072, 5,391,550 and 5,240,961, the teachings of whichare incorporated herein by reference in their entirety.

The phrase “sufficient quantity of a monoterpene suitable to solubilize”is therefore intended to mean that that amount of a monoterpene thatwill dissolve a component under a given set of conditions, generally,those at ambient temperature. This determination should be understood byone skilled in the art and can be determined by methods known in theart, such as by solubility studies.

One of the particular advantages of utilizing monoterpenes incombination with CoQ-10 and/or an amino acid is that the ingredient isdissolved by the monoterpene. That is, many formulations currently inthe marketplace have CoQ-10, for example, present as a suspension; asituation where not all the CoQ-10 is dissolved. This reduces efficacyand the bioavailability of the CoQ-10 and/or the amino acid (ifpresent). The present invention eliminates this disadvantage bysolubilizing the components in the monoterpene.

A particular advantage in using monoterpenes is that the CoQ-10 does nothave to be heated to dissolve into solution. This is important so thatthe CoQ-10 does not degrade upon dissolution.

The term “monoterpene” as used herein, refers to a compound having a10-carbon skeleton with non-linear branches. A monoterpene refers to acompound with two isoprene units connected in a head-to-end manner. Theterm “monoterpene” is also intended to include “monoterpenoid”, whichrefers to a monoterpene-like substance and may be used loosely herein torefer collectively to monoterpenoid derivatives as well as monoterpenoidanalogs. Monoterpenoids can therefore include monoterpenes, alcohols,ketones, aldehydes, ethers, acids, hydrocarbons without an oxygenfunctional group, and so forth.

It is common practice to refer to certain phenolic compounds, such aseugenol, thymol and carvacrol, as monoterpenoids because their functionis essentially the same as a monoterpenoid. However, these compounds arenot technically “monoterpenoids” (or “monoterpenes”) because they arenot synthesized by the same isoprene biosynthesis pathway, but rather byproduction of phenols from tyrosine. However, common practice will befollowed herein.

Suitable examples of monoterpenes include, but are not limited to,limonene, pinene, cintronellol, terpinene, nerol, menthane, carveol,S-linalool, safrol, cinnamic acid, apiol, geraniol, thymol, citral,carvone, camphor, etc. and derivatives thereof. For information aboutthe structure and synthesis of terpenes, including terpenes of theinvention, see Kirk-Othmer Encyclopedia of Chemical Technology, Mark, etal., eds., 22:709–762 3d Ed (1983), the teachings of which areincorporated herein in their entirety.

In particular, suitable limonene derivatives include perillyl alcohol,perillic acid, cis-dihydroperillic acid, trans-dihydroperillic acid,methyl esters of perillic acid, methyl esters of dihydroperillic acid,limonene-2-diol, uroterpenol, and combinations thereof.

Formulation of the CoQ-10 and/or an amino acid can be accomplished bymany methods known in the art. For example, the solubilized CoQ-10 canbe formulated in a suspension, an emulsion, an elixir, a solution, acaplet that harbors the liquid, or in a soft gelatin capsule. Often theformulation will include an acceptable carrier, such as an oil, or othersuspending agent.

Suitable carriers include but are not limited to, for example, fattyacids, esters and salts thereof, that can be derived from any source,including, without limitation, natural or synthetic oils, fats, waxes orcombinations thereof. Moreover, the fatty acids can be derived, withoutlimitation, from non-hydrogenated oils, partially hydrogenated oils,fully hydrogenated oils or combinations thereof. Non-limiting exemplarysources of fatty acids (their esters and salts) include seed oil, fishor marine oil, canola oil, vegetable oil, safflower oil, sunflower oil,nasturtium seed oil; mustard seed oil, olive oil, sesame oil, soybeanoil, corn oil, peanut oil, cottonseed oil, rice bran oil, babassu nutoil, palm oil, low erucic rapeseed oil, palm kernel oil, lupin oil,coconut oil, flaxseed oil, evening primrose oil, jojoba, tallow, beeftallow, butter, chicken fat, lard, dairy butterfat, shea butter orcombinations thereof.

Specific non-limiting exemplary fish or marine oil sources includeshellfish oil, tuna oil, mackerel oil, salmon oil, menhaden, anchovy,herring, trout, sardines or combinations thereof. In particular, thesource of the fatty acids is fish or marine oil (DHA or EPA), soybeanoil or flaxseed oil. Alternatively or in combination with one of theabove identified carriers, beeswax can be used as a suitable carrier, aswell as suspending agents such as silica (silicon dioxide).

The formulations of the invention are considered dietary supplementsuseful to the increase the amounts of CoQ-10 and/or amino acid(s) inindividuals in need thereof.

Alternatively, the formulations of the invention are also considered tobe nutraceuticals. The term “nutraceutical” is recognized in the art andis intended to describe specific chemical compounds found in foods thatmay prevent disease. CoQ-10 and amino acids are such compounds.

The formulations of the invention can further include variousingredients to help stabilize, or help promote the bioavailability ofthe CoQ-10 and/or amino acid(s), or serve as additional nutrients to anindividual's diet. Suitable additives can include vitamins andbiologically-acceptable minerals. Non-limiting examples of vitaminsinclude vitamin A, B vitamins, vitamin C, vitamin D, vitamin E, vitaminK and folic acid. Non-limiting examples of minerals include iron,calcium, magnesium, potassium, copper, chromium, zinc, molybdenum,iodine, boron, selenium, manganese, derivatives thereof or combinationsthereof. These vitamins and minerals may be from any source orcombination of sources, without limitation. Non-limiting exemplary Bvitamins include, without limitation, thiamine, niacinamide, pyridoxine,riboflavin, cyanocobalamin, biotin, pantothenic acid or combinationsthereof.

Vitamin(s), if present, are present in the composition of the inventionin an amount ranging from about 5 mg to about 500 mg. More particularly,the vitamin(s) is present in an amount ranging from about 10 mg to about400 mg. Even more specifically, the vitamin(s) is present from about 250mg to about 400 mg. Most specifically, the vitamin(s) is present in anamount ranging from about 10 mg to about 50 mg. For example, B vitaminsare in usually incorporated in the range of about 1 milligram to about10 milligrams, i.e., from about 3 micrograms to about 50 micrograms ofB12. Folic acid, for example, is generally incorporated in a range ofabout 50 to about 400 micrograms, biotin is generally incorporated in arange of about 25 to about 700 micrograms and cyanocobalamin isincorporated in a range of about 3 micrograms to about 50 micrograms.

Mineral(s), if present, are present in the composition of the inventionin an amount ranging from about 25 mg to about 1000 mg. Moreparticularly, the mineral(s) are present in the composition ranging fromabout 25 mg to about 500 mg. Even more particularly, the mineral(s) arepresent in the composition in an amount ranging from about 100 mg toabout 600 mg.

Various additives can be incorporated into the present compositions.Optional additives of the present composition include, withoutlimitation, phospholipids, L-carnitine, starches, sugars, fats,antioxidants, amino acids, proteins, flavorings, coloring agents,hydrolyzed starch(es) and derivatives thereof or combinations thereof.

As used herein, the term “phospholipid” is recognized in the art, andrefers to phosphatidyl glycerol, phosphatidyl inositol, phosphatidylserine, phosphatidyl choline, phosphatidyl ethanolamine, as well asphosphatidic acids, ceramides, cerebrosides, sphingomyelins andcardiolipins.

As used herein, the term “antioxidant” is recognized in the art andrefers to synthetic or natural substances that prevent or delay theoxidative deterioration of a compound. Exemplary antioxidants includetocopherols, flavonoids, catechins, superoxide dismutase, lecithin,gamma oryzanol; vitamins, such as vitamins A, C (ascorbic acid) and Eand beta-carotene; natural components such as camosol, carnosic acid androsmanol found in rosemary and hawthorn extract, proanthocyanidins suchas those found in grapeseed or pine bark extract, and green tea extract.

The term “flavonoid” as used herein is recognized in the art and isintended to include those plant pigments found in many foods that arethought to help protect the body from cancer. These include, forexample, epi-gallo catechin gallate (EGCG), epi-gallo catechin (EGC) andepi-catechin (EC).

Any dosage form, and combinations thereof, are contemplated by thepresent invention. Examples of such dosage forms include, withoutlimitation, chewable tablets, elixirs, liquids, solutions, suspensions,emulsions, capsules, soft gelatin capsules, hard gelatin capsules,caplets, lozenges, chewable lozenges, suppositories, creams, topicals,ingestibles, injectables, infusions, health bars, confections, animalfeeds, cereals, cereal coatings, and combinations thereof. Thepreparation of the above dosage forms are well known to persons ofordinary skill in the art.

For example, health bars can be prepared, without limitation, by mixingthe formulation plus excipients (e.g., binders, fillers, flavors,colors, etc.) to a plastic mass consistency. The mass is then eitherextended or molded to form “candy bar” shapes that are then dried orallowed to solidify to form the final product.

Soft gel or soft gelatin capsules can be prepared, for example, withoutlimitation, by dispersing the formulation in an appropriate vehicle(e.g. rice bran oil, monoterpene and/or beeswax) to form a highviscosity mixture. This mixture is then encapsulated with a gelatinbased film using technology and machinery known to those in the soft gelindustry. The industrial units so formed are then dried to constantweight. Typically, the weight of the capsule is between about 100 toabout 2500 milligrams and in particular weigh between about 1500 andabout 1900 milligrams, and more specifically can weigh between about1500 and about 2000 milligrams.

For example, when preparing soft gelatin shells, the shell can includebetween about 20 to 70 percent gelatin, generally a plasticizer andabout 5 to about 60% by weight sorbitol. The filling of the soft gelatincapsule is liquid (principally limonene, in combination with rice branoil and/or beeswax if desired) and can include, apart form theantioxidant actives, a hydrophilic matrix. The hydrophilic matrix, ifpresent, is a polyethylene glycol having an average molecular weight offrom about 200 to 1000. Further ingredients are optionally thickeningagents. In one embodiment, the hydrophilic matrix includes polyethyleneglycol having an average molecular weight of from about 200 to 1000, 5to 15% glycerol, and 5 to 15% by weight of water. The polyethyleneglycol can also be mixed with propylene glycol and/or propylenecarbonate.

In another embodiment, the soft gel capsule is prepared from gelatin,glycerine, water and various additives. Typically, the percentage (byweight) of the gelatin is between about 30 and about 50 weight percent,in particular between about 35 and about weight percent and morespecifically about 42 weight percent. The formulation includes betweenabout 15 and about 25 weight percent glycerine, more particularlybetween about 17 and about 23 weight percent and more specifically about20 weight percent glycerine.

The remaining portion of the capsule is typically water. The amountvaries from between about 25 weigh percent and about 40 weight percent,more particularly between about 30 and about 35 weight percent, and morespecifically about 35 weight percent. The remainder of the capsule canvary, generally, between about 2 and about 10 weight percent composed ofa flavoring agent(s), sugar, coloring agent(s), etc. or combinationthereof. After the capsule is processed, the water content of the finalcapsule is often between about 5 and about 10 weight percent, moreparticularly 7 and about 12 weight percent, and more specificallybetween about 9 and about 10 weight percent.

As for the manufacturing, it is contemplated that standard soft shellgelatin capsule manufacturing techniques can be used to prepare thesoft-shell product. Examples of useful manufacturing techniques are theplate process, the rotary die process pioneered by R. P. Scherer, theprocess using the Norton capsule machine, and the Accogel machine andprocess developed by Lederle. Each of these processes are maturetechnologies and are all widely available to any one wishing to preparesoft gelatin capsules.

Typically, when a soft gel capsule is prepared, the total weight isbetween about 250 milligrams and about 2.5 gram in weight, e.g., 400–750milligrams. Therefore, the total weight of additives, such as vitaminsand antioxidants, is between about 80 milligrams and about 2000milligrams, alternatively, between about 100 milligrams and about 1500milligrams, and in particular between about 120 milligrams and about1200 milligrams. In particular, the soft gel capsule typically weighsbetween about 1000 milligrams and 1300 milligrams, wherein thepercentage fill is about 50% of the entire weight of the capsule, i.e.,from about 500 to about 650 milligrams fill weight. The fill weightincludes the active ingredient(s), solubilizing agents, etc.

Preparation of the soft gel capsules was accomplished by methods wellknown in the art including, but not limited to those describedthroughout the specification and in U.S. Pat. Nos. 6,616,942, 6,623,734and pending U.S. Ser. Nos. 10/035,753 and 09/825,920, the contents ofwhich are incorporated herein by reference in their entirety.

For example, a soft gel capsule can be prepared by mixing a 35% solutionof CoQ-10 (by weight) and a 26% solution of an amino acid, such ascarnitine (by weight), and limonene (w/w/w) (e.g., 104 milligrams ofCoQ-10, 228 milligrams carnitine tartrate in 470.5 milligrams oflimonene) with between about 0.01 grams and about 0.4 grams (e.g., 0.1grams) tocopherol, between about 200 grams and about 250 grams (e.g.,225 grams) rice bran oil and between about 0.01 grams and about 0.5grams betacarotene (e.g. about 0.02 grams). The mixture is then combinedwith encapsulated within a gelatin capsule as described above.

The present invention also provides packaged formulations of amonoterpene with CoQ-10 and/or an amino acid such as carnitine andinstructions for use of the tablet, capsule, elixir, etc. Typically, thepackaged formulation, in whatever form, is administered to an individualin need thereof that requires an increase in the amount of CoQ-10 and/orthe amino acid in the individual's diet. Typically, the dosagerequirement is between about 1 to about 4 dosages a day.

CoQ-10 has been implicated in various biochemical pathways and issuitable for the treatment of cardiovascular conditions, such as thoseassociated with, for example, statin drugs that effect the body'sability to product CoQ-10 naturally. CoQ-10 has also been implicated invarious periodontal diseases. Furthermore, CoQ-10 has been implicated inmitochondrial related diseases and disorders, such as the inability toproduct acetyl coenzyme A, neurological disorders, for example, such asParkinson's disease and, Prater-Willey syndrome.

The following examples are intended to be illustrative only and shouldnot be considered limiting.

EXAMPLES

Formulations of CoQ-10 and an amino acid, such as carnitine, can beprepared in the following ratios by mixing the components together andthen placing into a soft gel capsule.

Component Example 1 Example 2 CoQ-10 104.09 mg 104.09 mg Carnitinetartrate 227.69 mg 196.02 mg Mixed Tocopherols 269.03 mg 269.03 mg (372IU/g) Rice Bran Oil 176.02 mg 0 Natural Beta Carotene  10.05 mg  10.05mg (20% by weight) Yellow Beeswax  20.0 mg 0 D-limonene    0 mg 227.69mg Total weight   796 mg   796 mg

Example 2 demonstrates that the use of limonene solubilizes CoQ-10 andcarnitine tartrate without the requirement of beeswax and/or rice branoil being present. Examples 1 and 2 could be incorporated into soft gelcapsules by standard methods known in the art and as described herein.

Component Example 3 Example 4 CoQ-10 104.08 mg 104.08 mg Carnitine(tartrate) 4.50 mg 78 mg D-Limonene 191.42 mg 167.92 mg 5–67 Tocopherol50 mg (50 IU) 100 mg (100 IU)

Examples 3 and 4 demonstrate that CoQ-10 and carnitine tartrate can besolubilized in scalable quantities. Additives, such as EPAX 2050 TG (anω-3 oil; 20% EPA/50% DHA as triglycerides, remainder fattyacid/triglycerides; Pronova Biocare) and tocopherols (5-67 Tocopherol;BD Industries) can easily be incorporated into such limonene containingformulations. The resultant mixtures contained approximately 100 mg ofCoQ-10 and ranges of carnitine (based on carnitine tartrate) per softgel capsule. Preparation of the soft gel capsules was accomplished bymethods well known in the art and as described herein.

Although the present invention has been described with reference topreferred embodiments, persons skilled in the art will recognize thatchanges may be made in form and detail without departing from the spiritand scope of the invention.

All literature and patent references cited throughout the applicationare incorporated by reference into the application for all purposes.

What is claimed is:
 1. A composition comprising: coenzyme Q-10 andcarnitine; a sufficient quantity of limonene suitable to solubilize saidcoenzyme Q-10 and carnitine; and an acceptable carrier.
 2. Thecomposition of claim 1, wherein said coenzyme Q-10 is selected from thegroup consisting of coenzyme Q-10, reduced coenzyme Q-10 andsemi-reduced coenzyme Q-10.
 3. The composition of claim 1, wherein saidcomposition is in the form of a solution, an elixir, a suspension, or acaplet.
 4. The composition of claim 3, wherein said caplet is a softgelatin tablet or capsule.
 5. The composition of claim 4, wherein saidsoft gelatin tablet or capsule further comprises rice bran oil orbeeswax.
 6. The composition of claim 1, wherein said coenzyme Q-10 issolubilized in an amount of at least about 0.1% by weight to about 45%by weight.
 7. The composition of claim 6, wherein said coenzyme Q-10 issolubilized in an amount of least about 5% to about 40% by weight. 8.The composition of claim 1, wherein said carnitine is solubilized in anamount of at least about 0.1% by weight to about 20% by weight.
 9. Thecomposition of claim 8, wherein said carnitine is solubilized in anamount of at least about 0.5% by weight to about 10% by weight.
 10. Thecomposition of claim 1, further comprising vitamin E.
 11. Thecomposition of claim 1, further comprising a seed oil.
 12. Thecomposition of claim 1, further comprising a fish oil.
 13. Thecomposition of claim 1, further comprising an antioxidant.
 14. Thecomposition of claim 4, wherein said soft gelatin tablet or capsulefurther comprises an antioxidant.
 15. A packaged nutraceuticalformulation comprising: coenzyme Q-10 and carnitine, and a sufficientquantity of limonene, wherein said formulation is encapsulated in agelatin capsule, and instructions for use thereof.
 16. The packagednutraceutical formulation of claim 15, wherein said coenzyme Q-10 isselected from the group consisting of coenzyme Q-10, reduced coenzymeQ-10 and semi-reduced coenzyme Q-10.
 17. The packaged nutraceuticalformulation of claim 15, wherein said carnitine is solubilized in anamount of at least about 0.1% by weight to about 20% by weight.
 18. Thepackaged nutraceutical formulation of claim 17, wherein said carnitineis solubilized in an amount of at least about 0.5 % by weight to about10 % by weight.
 19. The composition of claim 4, wherein said coenzymeQ-10 is solubilized in an amount of at least about 0.1% by weight toabout 45% by weight.
 20. The composition of claim 19, wherein saidcoenzyme Q-10 is solubilized in an amount of least about 5% to about 40%by weight.
 21. The composition of claim 4, wherein said carnitine issolubilized in an amount of at least about 0.1% by weight to about 20%by weight.
 22. The composition of claim 21, wherein said carnitine issolubilized in an amount of at least about 0.5% by weight to about 10%by weight.
 23. The packaged nutraceutical formulation of claim 15,wherein said gelatin capsule is a soft gelatin capsule.
 24. The packagednutraceutical formulation of claim 15, wherein said coenzyme Q-10 issolubilized in an amount of at least about 0.1% by weight to about 45%by weight.
 25. The packaged nutraceutical formulation of claim 15,wherein said coenzyme Q-10 is solubilized in an amount of at least about0.5% by weight to about 40% by weight.